The objective of this research is to distinguish different kinds of epidermal cells on the basis of their cell surface glycoproteins. The long-term goal is an understanding of the control mechanisms operative in epidermal differentiation and neoplastic transformation. A comparative study of the glycoprotein changes associated with several diseases of epidermal differentiation has been completed using the gel overlay technique with six different iodinated lectins; it is being extended to premalignant and malignant tissue. We have isolated two Con A binding glycoproteins from human epidermis, one of which is found in the stratum corneum and the other in the viable cell layers. We have produced antibodies to both and are proceeding with their characterization. We are also targeting additional glycoproteins. We have observed that the cell surface changes in normal epidermal cells going from low to metabolic levels of Ca2+ are duplicated in malignantcells at higher Ca2+ concentrations. Contrary to findings in fibroblasts, nonmalignant epidermal cells are more severely affected by tunicamycin than are the corresponding malignant cells. The effects of interferon, retinoic acid, and tumor promoters on malignant and nonmalignant keratinocytes have been examined with Con A and will be pursued with other lectins. (A)